PXD012736

PXD012736 is an original dataset announced via ProteomeXchange.

Title	Attenuated palmitoylation of serotonin receptor 5-HT1A in brain affects receptor functions and triggers depressive symptoms
Description	The serotonergic system and in particular serotonin 1A receptor (5-HT1AR) are critically implicated in major depressive disorder (MDD), although underlying mechanisms remain enigmatic. Here we demonstrated that 5-HT1AR is palmitoylated in human and rodent brains and identified ZDHHC21 as a major palmitoyl-transferase, whose depletion reduced palmitoylation and consequently signaling functions of 5-HT1AR. Two rodent models for depression show reduced brain ZDHHC21 expression in conjunction with attenuated 5-HT1AR palmitoylation. Moreover, selective knock-down of ZDHHC21 in murine forebrain by itself sufficed to provoke depressive symptoms, demonstrating a causal relationship between 5-HT1AR palmitoylation and depression. Regarding the underlying mechanism, we identified the microRNA miR-30e as a negative regulator of Zdhhc21 expression. By analysis of the post-mortem samples from suicide MDD victims we also found ZDHHC21 expression as well as palmitoylation of 5-HT1AR to be specifically reduced within the prefrontal cortex (PFC), a brain area critically involved in the pathogenesis of depressive symptoms. Our study provides evidence for transcriptional downregulation of 5-HT1AR palmitoylation as a central mechanism in the etiology of depression and even suicide, in effect making the restoration of 5-HT1AR palmitoylation a promising clinical strategy for the treatment of major depressive disorder.
HostingRepository	PRIDE
AnnounceDate	2019-07-16
AnnouncementXML	Submission_2019-07-16_00:38:12.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Monika Zareba-Koziol
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	N-ethylmaleimide derivatized cysteine; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-15 08:03:14	ID requested
⏵ 1	2019-07-16 00:38:13	announced

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: Serotonin 5-HT1A receptor, depression, suicide, palmitoylation, ZDHHC, miRNA

Wlodarczyk Jakub
contact affiliation	Cell Biophysics, Nencki Institute, Warsaw, Poland
contact email	j.wlodarczyk@nencki.gov.pl
lab head
Monika Zareba-Koziol
contact affiliation	Laboratory of Cell Biophysics, Nencki Institute of Experimental Biology, PAS
contact email	m.zareba-koziol@nencki.gov.pl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/07/PXD012736

PRIDE project URI

• PRIDE
  1. PXD012736
     1. Label: PRIDE project
     2. Name: Attenuated palmitoylation of serotonin receptor 5-HT1A in brain affects receptor functions and triggers depressive symptoms